Heart Failure Specialized Center of Research (SCOR) is a multidisciplinary, interdepartmental clinical and basic research program that is directed at the reduction of death and disability from congestive heart failure. This proposed research program uses state of the art molecular biological techniques to address clinical, pharmacological and physiological questions relevant to the management of heart failure patients. The clinical component of this application encompasses research into the pathophysiology of exercise intolerance in ambulatory patients with congestive heart failure. The fundamental component encompasses research into the most fundamental biological processes by the mechanism by which calmodulation overexpression causes cardiac myocyte hypertrophy and hyperplasia; the mechanisms underlying the activation and desensitization of alpha- adrenergic receptors; the mechanisms underlying adenosine receptor mediated transmembrane signalling in vascular smooth muscle cells; and the mechanism of gating and drug binding to a transient outward potassium channel that plays an important role in cardiac repolarization. This integrated effort is aimed at translating the results of the applicant's diverse research efforts concerning the pathophysiology, clinical, pharmacologic and surgical therapy into the clinic to reduce death and disability from congestive heart failure.